During the past year we have made significant findings in several different areas. In the area of genetics of auditory pitch perception, we have focused on estimating the genetic contribution to the variation in human musical pitch perception. Our measure of this function is the Distorted Tunes Test (DTT), in which subjects judge the correctness of a series of 26 short familiar melodies that are presented either correctly or incorrectly, where they contain notes of the wrong pitch. Using the DTT, we performed a large twin study, involving 340 pairs of twins. The twins also completed the Five Minute Hearing Test, a screening questionnaire promulgated by the American Academy of Otolaryngology which has been correlated with pure tone audiometry and other careful measures of hearing. The results showed that variation in DTT scores is largely due to genetic factors, with heritabilities estimated at 70-80%. In addition, subjects? DTT scores were virtually uncorrelated with their scores on the Five Minute Hearing Test, suggesting that this heritable variation is expressed outside the parts of the hearing system measured by traditional audiology. These results were reported in Drayna et al. Science 291:1969-1972 (2001). Significant progress was also made in our studies on the genetics of stuttering. We completed statistical analysis of our genome-wide linkage survey in our initial group of 70 families containing multiple individuals who stutter beyond young childhood. Significant evidence for linkage to markers on chromosome 18 was discovered, with much of the statistical support coming from a single large 3-generation kindred in our family sample. Other families in aggregate showed weak positive LOD scores at this location, and thus currently it is not clear what contribution this gene makes to familial stuttering across the broad population. A manuscript describing these results has been submitted for publication. This location is an important first step in our efforts to identify this gene itself, which would provide the first insight into a fundamental cause of stuttering. We have also recorded progress in our studies of inherited deficits in the sense of bitter taste. Our model system is the classical substance phenylthiocarbamide (PTC), which tastes intensely bitter to the majority of the population, but is largely tasteless to 25-30% of individuals of European ancestry. We have determined PTC taste thresholds in over 250 members of 26 C.E.P.H. genetic reference families, large nuclear families that were used to construct the normal human genetic linkage map in the 1980?s. As a result of this effort, genotype information is available at over 3000 marker loci in the individuals in these families. Using this existing information we have performed linkage studies that have initially challenged and subsequently revised the textbook view of this trait as a simple single-locus Mendelian recessive. We have shown that one such locus is at work in a minority of families, and that this locus resides on the long arm of chromosome 7. However, many families show linkage to a number of loci on other chromosomes. In these families, we have discovered evidence that the non-taster trait is inherited in a non-Mendelian fashion. Current studies are aimed at identifying the specific causative genes for this deficit.